Prenatal Ethanol Exposure and Postnatal Environmental Intervention Alter Dopaminergic Neuron and Microglia Morphology in the Ventral Tegmental Area During Adulthood.

BACKGROUND: Prenatal ethanol exposure (PE) impairs midbrain dopaminergic (DA) neuron function, which might contribute to various cognitive and behavioral deficits, including attention deficits and increased addiction risk, often observed in individuals with fetal alcohol spectrum disorders. Currently, the underlying mechanisms for PE-induced deficits are unclear. PE could lead to neuroinflammation by activating microglia, which play an important role in synaptic function. In the present study, we investigated PE effects on microglial activation and DA neuron density and morphology in the ventral tegmental area (VTA). Since postnatal environmental enrichment can reduce neuroinflammation and ameliorate several PE-induced behavioral deficits, we examined if a postnatal environmental intervention strategy using neonatal handling and postweaning complex housing could reverse PE effects on VTA DA neurons and microglia. METHODS: Pregnant rats received 0 or 6 g/kg/d ethanol by 2 intragastric intubations on gestation days 8 to 20. After birth, rats were reared in the standard laboratory or enriched condition. Male adult rats (8 to 12 weeks old) were used for immunocytochemistry. RESULTS: The results showed that PE decreased VTA DA neuron body size in standardly housed rats. Moreover, there was a significant decrease in numbers of VTA microglial branches and junctions in PE rats, suggesting morphological activation of microglia and possible neuroinflammation. The PE effects on microglia were normalized by postnatal environmental intervention, which also decreased the numbers of microglial branches and junctions in control animals, possibly via reduced stress. CONCLUSIONS: Our findings show an association between PE-induced morphological activation of microglia and impaired DA neuron morphology in the VTA. Importantly, postnatal environmental intervention rescues possible PE-induced microglial activation. These data support that environmental intervention can be effective in ameliorating cognitive and behavioral deficits associated with VTA DA neuron dysfunctions, such as attention deficits and increased addiction risk.

Volumetric Nephrogram Represents Renal Function and Complements Aortic Anatomic Severity Grade in Predicting EVAR Outcomes.

INTRODUCTION: Chronic kidney disease (CKD) is a predictor of poor outcomes for patients undergoing endovascular aortic aneurysm repair (EVAR). Anatomic severity grade (ASG) represents a quantitative mechanism for assessing anatomical suitability for endovascular aortic repair. Anatomic severity grade has been correlated with repair outcomes and resource utilization. The purpose of this study was to identify a novel renal perfusion metric as a way to assist ASG with predicting EVAR outcomes. METHODS: Retrospective review of a prospectively maintained database identified elective infrarenal aortic aneurysm repair cases. Anatomic grading was undertaken by independent reviewers. Using volumetric software, kidney volume, and a novel measure of kidney functional volume, the volumetric nephrogram (VN) was recorded. Systematic evaluation of the relationship of kidney volume and VN to CKD and ASG was undertaken using linear regression and receiver-operator statistical tools. RESULTS: A total of 386 cases with patient and anatomic data were identified and graded. Mean age was 72.9 ± 0.4 years. Renal volume <281 mL correlated with CKD (area under the curve [AUC] = .708; P ≤ .0001). Volumetric nephrogram <22.5 HU·L correlated with CKD (AUC = 0.764; P ≤ .0001). High (≥15) ASG scores correlated with both renal volume (AUC = .628; P ≤ .0001) and VN (AUC = .628; P ≤ .0001). Regression analysis demonstrated a strong, inverse relationship between ASG and VN ( R2 = .95). CONCLUSION: These data demonstrate that VN is a strong predictor of CKD in a large database of patients undergoing elective aneurysm repair. We demonstrate an inverse relationship between renal function and ASG that has not been previously described in the literature. Additionally, we have shown that VN complements ASG as a model of overall cardiovascular health and atherosclerotic burden. Outcomes in patients with poor renal function may be related to anatomical issues in addition to well-described systemic ramifications.

Aspirin use is associated with decreased radiologically-determined thrombus sac volume in abdominal aortic aneurysms.

Introduction Formation and renewal of intramural thrombus is associated with inflammation, and contributes to the complexity of aneurysm repair. Current cardiovascular pharmacotherapy includes several inflammatory modulators such as aspirin, statins, clopidogrel, and angiotensin-converting enzyme inhibitors. The purpose of our study was to investigate the effect of these inflammatory modulators on radiographically-determined thrombus sac volume. Methods Pre-operative computed tomography scans were reviewed in patients who underwent elective infrarenal aortic aneurysm repair. Thrombus sac volume was obtained using a Hounsfield unit restricted region growth algorithm. Co-morbid conditions such as diabetes mellitus and post-operative complications were evaluated compared to thrombus sac volume. Receiver-operator characteristic curves were generated for thrombus sac volume and patients on the various cardiovascular pharmacotherapies. Results A total of 266 patients (mean age = 72.6 ± 0.6 years; mean thrombus sac volume = 58.7 (34.4-89.0) cm3) were identified. Acetylsalicylic acid use was associated with a decreased thrombus sac volume ≤50 cm3 (AUC = 0.616, p = 0.013) whereas statins ( p = 0.26), angiotensin-converting enzyme inhibitors ( p = 0.46), and clopidogrel ( p = 0.62) had no correlation to thrombus sac volume. Diabetes mellitus was not associated with thrombus sac volume ( p = 0.31). Conclusion Acetylsalicylic acid use is associated with decreased thrombus sac volume in a patient population undergoing elective abdominal aortic aneurysms repair. The effect of acetylsalicylic acid over other anti-inflammatory and anti-platelet agents is possibly attributable to its distinct mechanism of cyclooxygenase-1 inhibition. Diabetes mellitus, a known correlate of aneurysm incidence, is not associated with thrombus burden. The potential to alter aneurysm thrombus volume, thereby affecting aneurysm morphology, may yield a more favorable aneurysmal repair.